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Biomedical subjects

J B Gavin

Publications and source records attributed to J B Gavin.

At least 73 records · Page 4Linked to original sources
PubMed1985

Cardiac performance of isolated beating hearts obtained from rats anesthetized by three different agents.

Two functional performance parameters (heart rate and coronary flow rate) of three groups of six isolated beating hearts obtained from rats anesthetized by inhalation of diethyl ether in air, injection intraperitoneally of sodium pentobarbital (60mg/kg) or intravenously of alphaxalone/alphadolone (15mg/kg) were compared. Differences were small, but alphaxalone-alphadolone showed lowest stable mean coronary flow rate and diethyl ether the widest variation between animals. No significant difference in function was found between ether and pentobarbital, currently the two most widely used methods. But, pentobarbital showed higher stable functional performance and least variation between animals. We conclude that pentobarbital is the most useful of these three agents for obtaining hearts for perfusion as isolated beating organs, and that alphaxalone-alphadolone is clearly less suitable.

Anesthesia↗
PubMed1985

Graft detachment, a cause of incompetence in stent-mounted aortic valve allografts.

The detachment of allograft tissue from supporting stent posts has been a common mode of failure of stent-mounted aortic allografts. In an effort to reduce the localized stress loading on the tissue at the top of the stent posts, two changes were introduced to the previous fabrication protocol followed by Green Lane Hospital. Specifically, they were the use of a flexible acetyl-copolymer stent and covering of the peripheral attachment sutures with a bias strip of Dacron cloth. This study showed that these changes did not reduce the incidence of allograft failure caused by graft detachment. Unexpectedly, covering antibiotic-treated allograft tissue with a bias strip actually increased the likelihood of failure of the valve, by accelerating the biological degradation of the underlying graft aortic wall. The weakened aortic wall tissue was consequently less able to resist the high stress loadings at the top of the stent posts where detachment first occurred.

Adult↗
PubMed1984

Morphological identification of functional capillaries in the myocardium.

This study used acrylic resin as an intravascular marker to demonstrate functional myocardial capillaries after fixation by perfusion. Eight rat hearts were excised and allowed to function as isolated organs perfused with oxygenated Krebs-Henseleit buffer (37 degrees C, 10 kPa) for 10 min. Four were fixed by perfusion (4 min) with 2.5% glutaraldehyde at the same temperature and pressure and then immersion fixed (24 hr). The other four hearts were perfused with 0.2% procaine HCl for 30 sec just prior to similar fixation. Polymerizing low viscosity acrylic resin was injected at 10 kPa pressure into the fixed vascular beds and allowed to cure, then transmural blocks of left ventricular myocardium were prepared for scanning electron microscopy. Total initial coronary flow of fixative after procaine treatment was significantly increased, while in untreated hearts the initial fixative flow rate was closely similar to that of oxygenated buffer. The pattern of capillary perfusion was assessed, and the percentage of capillary profiles filled by acrylic resin were calculated. Following procaine treatment, 95.2% of capillaries appeared functional, whereas without procaine arrest, only 62.0% of capillaries allowed the passage of resin. This study indicates that perfusion fixation with glutaraldehyde stabilizes myocardial structure so that the proportion of functional capillary pathways remains closely similar to that in the beating heart and so that such functional capillaries can be identified in morphological preparations by using a low viscosity intraluminal resin marker.

Acrylic Resins↗
PubMed1984

The influence of the no-reflow phenomenon on reperfusion and reoxygenation damage and enzyme release from anoxic and ischaemic isolated rat hearts.

Eighty isolated rat heart preparations were used to study relationships among creatine kinase (CK) release, the loss of vascular competence (no-reflow), and the distribution of morphological changes across the left ventricular wall which occur during 60 min global ischaemia or anoxia and following subsequent oxygenated reperfusion. Hearts were either fixed with glutaraldehyde for light and electron microscopy or were injected with 1% fluorescein to define the distribution of perfusable vessels. The extent of no-reflow in half of the hearts was reduced experimentally by maintaining the diastolic volume of the left ventricular lumen during ischaemia and anoxia with a water-filled balloon. The amount of CK released during 20 min of reoxygenation or reperfusion was inversely proportional to the extent of the no-reflow area observed just prior to reoxygeneration, and also reflected the transmural extent and the severity of myocardial cell damage. Extensive contraction band necrosis was only observed in reperfused regions of anoxic hearts. In isovolumic hearts reoxygenation caused no-reflow to develop in the ventricular myocardium, and this appeared to be associated with hypercontraction. Thus the no-reflow phenomenon has a profound effect on the transmural distribution of myocardial cell damage and enzyme release which follows post ischaemic reperfusion and post anoxic reoxygenation.

Animals↗
PubMed1984

The accuracy of hair cell counts in determining distance and position along the organ of Corti.

The relationship between the density of hair cells (cells/mm) and measured distance along the guinea pig organ of Corti was determined using light microscopy and the surface specimen technique. It was demonstrated that the density of inner hair cells (IHC; mean 92.0 +/- 2.4) and 1st row of outer hair cells (OHC1; mean 118.7 +/- 2.3) did not show significant variation along the organ of Corti except within 0.5-1.0 mm of the apex and base where there was considerable variation between animals in the density of cells. There was a close relationship between the accumulated number of either IHC or OHC1 and distance from the base along the organ of Corti. Distances estimated by hair cell counts were similar to those determined by direct measurement. It is concluded that hair cell counts can be used to reliably estimate distances along the organ of Corti where accurate direct measurement is not possible, such as in scanning electron microscopy.

Animals↗
PubMed1983

Changes in vascular morphology associated with the no-reflow phenomenon in ischaemic myocardium.

To investigate the pathogenesis of the reperfusion defect which develops in ischaemic myocardium, intravascular casts were prepared by injection of methyl methacrylate into the coronary arteries of isolated heparinised rat hearts. Using a scanning electron microscope, the vascular morphology following 60 min of global ischaemia at 37 degrees C was compared to that of non-ischaemic control hearts injected immediately after stopping perfusion with oxygenated Krebs-Henseleit buffer. Complete casts were obtained from control hearts and from all parts of ischaemic hearts except the subendocardial half of the left ventricular wall of ischaemic hearts where the blood vessels were not filled. At the border between the perfused subepicardial and unperfused left subendocardial regions, the resin which filled the radial penetrating arteries and their branches projected from the filled capillary plexus to an extent proportional to their diameter. Intravascular events such as erythrocyte plugging and thrombosis were excluded as causative factors by the use of a cell-free perfusate. Also, there was no morphological evidence that endothelial cell swelling or constriction of any particular population of vessels was involved. The observed pattern of vascular occlusion suggests that, during global ischaemia, blood vessels in the endocardial half of the left ventricular myocardium lose their ability to be reperfused because of extravascular compression.

Animals↗
PubMed1983

Histological assessment of orthotopic aortic valve leaflet allografts: its role in selecting graft pre-treatment.

Histopathological studies of human cardiac valve grafts recovered at autopsy or re-operation, together with long-term clinical follow-up of valve graft recipients, have indicated that the success of grafts is largely dependent upon the extent to which they are replaced by host fibrous connective tissue. To find the valve preparation technique with least inhibitory effect on tissue ingrowth after grafting, various sterilizing and storage procedures were evaluated using a series of aortic valve leaflet allografts in dogs. To facilitate evaluation, a method for rapidly assaying relative degrees of colonization of grafts was first devised. Application of this method has unequivocally identified a newly-formulated antibiotic solution as the pre-treatment most compatible with host tissue ingrowth.

Animals↗
PubMed1982

The influence of adenosine on the no-reflow phenomenon in anoxic and ischaemic hearts.

Adenosine and the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), separately and in combination, were added to the perfusate of isolated rat hearts which were then subjected to ischaemia or anoxia. The effect of these infusates on the vascular competence of the myocardium subjected to oxygen deprivation of from 15-90 min was compared to control hearts. Vascular competence at selected time intervals was assessed from the distribution of injected. 1% sodium fluorescein in the cut surface of the ventricles. A region of non-perfusion surrounding the left ventricular lumen and involving 25% of the ventricular myocardium developed within 15 min of anoxic perfusion, with little change thereafter. Adenosine had no significant effect on this. The no-reflow phenomenon following ischaemia had similar distribution, but developed more slowly and eventually involved twice as much of the myocardium (59% after 90 min). Surprisingly, pre-treatment with adenosine greatly increased (from 14-46%) the extent of no-reflow after 30 min of ischaemia. Pre-treatment with EHNA caused a slight reduction (59-43%) in its extent but only after 60 min. Thus the no-reflow phenomenon which developed in ischaemic myocardium is unlikely to be due to the reduced vasodilatory action of adenosine.

Adenine↗
PubMed1982

A comparison of the effects of ischemia and of selective occlusion of capillaries, pre-capillaries and terminal arterioles on coronary reperfusion.

To study the 'no-reflow' phenomenon is ischemic myocardium, the effects of ischemia and selective embolic blockade of capillaries, precapillaries and terminal arterioles were compared in isolated rat hearts. Hearts received oxygenated Krebs-Henseleit buffer for 10 min via an aortic cannula, and then coronary perfusion was stopped. The pattern and extent of reperfusion after 15-90 min of global ischemia and after the injection of 9, 15 or 55 mu diameter microspheres were determined from the distribution of injected 6.7% fluorescein isothiocyanate-dextran in frozen transverse sections of the ventricles. Following ischemia, progressively larger subendocardial regions surrounding the left ventricle could not be reperfused. In contrast, embolic occlusion of capillaries, precapillaries or terminal arterioles caused a transmural reduction in perfusion and a fine linear or herringbone pattern of fluorescence. Sixty min of ischemia followed by microsphere injection had no effect on the subendocardial zone of no-reflow but much reduced the intensity of fluorescence elsewhere. Thus thrombosis, erythrocyte plugging and occlusion of capillaries, precapillaries or terminal arterioles are unlikely to be primary causes of the reperfusion defect which develops in ischemic myocardium.

Animals↗
PubMed1982

A method for the gross and microscopic investigation of vascular reperfusion in ischemic myocardium.

Fluorescein-isothiocyanate dextran (FITC-dextran; MW approximately 70,000) was used in isolated rat hearts to compare normal vascular perfusion of ventricular myocardium with the pattern and extent of reperfusion following 60 minutes of global ischemia. Its gross distribution in frozen transverse sections through the ventricles was similar to that of sodium fluorescein. However, unlike 0.1% sodium fluorescein, 6.7% FITC-dextran has a viscosity similar to that of blood, and its much higher molecular weight prevents its diffusion beyond the ischemically injured vessels. Furthermore, staining by the alcoholic periodic acid-Schiff technique enabled tracer distribution to be confirmed microscopically and distinguished competent from incompetent vessels in paraffin embedded material.

Animals↗
PubMed1981

Changes in the contractile state, fine structure and metabolism of cardiac muscle cells during the development of rigor mortis.

Transmural slices from the left anterior papillary muscle of dog hearts were maintained for 120 min in a moist atmosphere at 37 degrees C. At 15-min intervals tissue samples were taken for estimation of adenosine triphosphate (ATP) and glucose-6-phosphate (G6P) and for electron microscopic examination. At the same time the deformability under standard load of comparable regions of an adjacent slice of tissue was measured. ATP levels fell rapidly during the first 45 to 75 min after excision of the heart. During a subsequent further decline in ATP, the mean deformability of myocardium fell from 30 to 12% indicating the development of rigor mortis. Conversely, G6P levels increased during the first decline in adenosine triphosphate but remained relatively steady thereafter. Whereas many of the myocardial cells fixed after 5 min contracted on contact with glutaraldehyde, all cells examined after 15 to 40 min were relaxed. A progressive increase in the proportion of contracted cells was observed during the rapid increase in myocardial rigidity. During this late contraction the cells showed morphological evidence of irreversible injury. These findings suggest that ischaemic myocytes contract just before actin and myosin become strongly linked to maintain the state of rigor mortis.

Adenosine Triphosphate↗
PubMed1981

The effect of an isovolumic left ventricle on the coronary vascular competence during reflow after global ischemia in the rat heart.

During global ischemia in isolated rat hearts, the development of contracture, due to irreversible myofilament sliding, causes reduction of left ventricle luminal volume. Also, a considerable area of the myocardium cannot be reperfused after 1 hour's global ischemia. The purpose of this study was to reduce myofilament sliding by placing a fluid-filled isovolumic balloon in the left ventricular cavity of isolated rat hearts and assess the extent of reflow, after 60 minutes' ischemia, by perfusion of a 1% fluorescein tracer solution. Light and electron microscopy was used to determine the state of the vasculature and myofibrillar apparatus. In hearts without the left ventricular balloon (control) the ischemia produced a no-reflow zone comprising 45% of the myocardial wall. In contrast, if an isovolumic balloon was in place during the ischemic period, only 6% of the wall was involved. The volume of the capillary bed in the subendocardium of the control hearts was about 60% of that in th isovolumic hearts. In the isovolumic ("isometric") mode, ischemic contracture was associated with more severe myocardial cell injury than in the corresponding control ("isotonic") mode. Our results support the concept that intramyocardial pressure generated by ischemic contracture plays a major role in the production of the no-reflow phenomenon in globally ischemic rat hearts, and indicate that it is the series elastic component of cardiac muscle which imparts the stiffness necessary to prevent reopening of coronary vessels after a severe ischemic insult.

Animals↗
PubMed1981

The development of glomerular crescents in sheep.

Renal allografts were transplanted into 10 sheep with pre-existing experimental autoimmune glomerulonephritis. Serial biopsy samples were examined by light, electron and immunofluorescence microscopy. Sections were stained with naphthyl acetate to demonstrate non-specific esterase activity. Host antiglomerular basement membrane antibody was demonstrated in graft glomeruli only 30 min after transplantation, at which time up to 40% of glomeruli contained many intracapillary neutrophils. Three d after transplantation gaps in the glomerular basement membrane were evident and the urinary spaces contained polymorphonuclear leucocytes, red blood cells, large amounts of fibrin and occasional mononuclear leucocytes. These mononuclear cells had increased greatly in number by the 6th d and most contained phagocytic vacuoles. From the 7th to the 10th d the incidence of glomerular crescents increased to involve 80% of glomeruli, and the majority of cells within crescents showed phagocytic vacuoles. The number of cells exhibiting non-specific esterase activity increased markedly during the post-operative period and most were located within the urinary spaces. These results suggest that the majority of cells in the glomerular crescents were macrophages which were probably derived from blood monocytes.

Animals↗
PubMed1981

The effects of altered cation balance on the fine structure of hypoxic myocardial cells.

To determine whether the changes in intracellular/extracellular cation balance which develop in ischaemic myocardium are responsible for the fine structural changes seen in such tissue, thin slices of normal canine ventricle were incubated under hypoxic conditions at 37 degrees C and physiological pH in balanced salt solution (BSS), isotonic NaCl and isotonic KCl. Slices from each solution were fixed at 10-120 min intervals and examined by light and electron microscopy. For 60 min, tissue from both NaCl and KCl showed good overall preservation of cell architecture and only mild subcellular alterations including aggregation of nuclear chromatin, disappearance of glycogen granules, and swelling of sarcoplasmic reticulum. Tissue from BSS showed early development of intramitochondrial dense inclusions together with focal contraction-band damage similar to that seen in temporarily ischaemic, re-perfused heart muscle and at the margins of infarcts. These changes thus appear to be promoted by divalent cations. The progressive reversal of monovalent cation balance in an area of permanent and severe ischaemia does not appear to be a major determinant of fine structural change.

Animals↗
PubMed1981

The response of three inbred strains of rat to the carcinogen 1,2-dimethylhydrazine.

Rats of 3 inbred strains (DA, HS and AS2) were dosed with 1,2-dimethylhydrazine 2HCl (DMH) or saline by gavage weekly for 10 wk. DA and HS rats showed little overt toxic reaction but all AS2 rats died following DMH doses of 30 mg/kg. However, at 10 mg/kg 60% of AS2 rats survived the 30 wk experiment. All DA rats developed a high yield of adenocarcinoma of the bowel (means: males 6.8 tumours/large bowel and 0.8/small bowel; females 2.8/large and 0.08/small bowel) and one-third of the males developed tumours of the ear canal. A smaller proportion (52%) of HS rats developed tumours, specifically bowel tumours (means: male 1.4/large and 0.2/small bowel; females 0.4/large and 0.1/small bowel). Even on the lower dose of DMH AS2 rats showed extensive liver changes including cystic cholangioma (58%), angiosarcoma (25%) and hepatocellular carcinoma (8%) and 83% developed bowel tumours (means: males 2.3/large and 1.5/small bowel; females 3.5/large and 1.0/small bowel). The rapid induction and high yield of bowel tumours, the different toxicity of DMH in AS2 rats, and the differences in relative tumour density both between sexes and in the various segments of the bowel indicate the potential of these strains for studies of carcinogenesis in the bowel.

1,2-Dimethylhydrazine↗
PubMed1981

Recurrence of antiglomerular basement membrane glomerulonephritis in sheep renal allografts.

Renal autografts and allografts were placed in the necks of nephrectomized sheep. Some of the sheep which received allografts had been previously injected with human glomerular basement membrane to induce an autoimmune antiglomerular basement membrane glomerulonephritis. All previously diseased and normal recipient animals were treated wtih azathioprine and prednisone from the day before transplantation. The autografts and immunosuppressed allografts in normal recipients functioned similarly for the first 6 d, but subsequently the allografts deteriorated. Allografts in untreated recipients functioned for less than 3 d. Most (90%) of the allografts in previously diseased sheep developed heavy proteinuria and haematuria immediately after transplantation and their renal function remained low. These grafts showed severe glomerular lesions by the third day, and by 8 d more than 50% of the glomeruli contained crescents. At corresponding intervals the glomeruli of autografts and allografts in normal recipients showed only minor changes. These results demonstrate that antiglomerular basement antibodies circulating in the host at the time of transplantation are a significant threat to the survival of renal allografts.

Animals↗